Lice-repellant compositions

ABSTRACT

It has been discovered that terpenoids, especially terpenoid-alcohols (terpene-ols) and terpenoid-esters, and some aldehydes and ketones of terpenes, in a concentration of between 0.01% and 50% by weight, most preferably between 0.01% and 10%, are very good lice repellents. The active agent can be combined with a pharmaceutically and/or cosmetically acceptable carrier for topical administration, such as an aqueous or alcohol solution, a gel, cream, or a powder, and administered with or without additives such as other insect repellents, agents increasing solubility or delaying release of active agents, antimicrobials, antioxidants and fragrances. Examples demonstrate efficacy in in vitro and in in vivo testing.

This is a continuation of copending U.S. patent application Ser. No.07/642,806 filed on Jan. 18, 1991, now abandoned.

BACKGROUND OF THE INVENTION

Lice are a common pest which are widely distributed throughout the worldand infest both humans and animals. They are spread by contact and are aproblem even under relatively sanitary conditions.

Lice are insects about two to three millimeters in length. They lay eggscalled nits, which look like white grains of sand and are firmlyattached to the hairs by a cementlike excretion. The eggs generallyhatch in about eight to ten days at body temperature.

The common latin name for the whole family is "Anoplura". Human lice aredivided into two genera: Head lice, Pediculus capitis or Pediculushumanus capitis, and Body lice or Clothing lice, Pediculus humanushumanus or Pediculus corporis; and Pubic lice, Phthirius pubis. Lice arespread by crowding and common usage of clothing and combs. Initially,infestations result at most in irritation, which can lead to infectionof the irritated area, although there are at least three major diseasesthat are primarily transmitted by lice: epidemic typhus, trench feverand relapsing fever.

Lice on animals such as the dog are commonly associated with itching andare found under matted fur and around the ears, head, neck andshoulders. There are two types of lice, biting lice that feed on skinscales and sucking lice that feed on the dog's blood and can cause asevere anemia.

Special combs are used to remove the eggs from the hair. Lice areusually treated by application of an insecticidal product, such as 0.1to 2% pyrethroids with synergists, 68% benzyl benzoate, 6% DDT, 12%benzolaine and 14% Tween® 80, diluted 1:5. Several insecticides havealso been used for treatment of body lice, including 10% DDT, 1%lindane, and pyrethrum powders. Animals are treated with the insecticidethree to four times at ten day intervals, along with cleaning ordisposal of associated bedding. It would clearly be preferable to have atreatment which prevents infestation, rather than a treatment afterinfestation of either a person or an animal Although a number of insectrepellents have been developed, most are relatively specific to aparticular type of insect, such as mosquitos, or smell bad, which wouldlimit usefulness under routine conditions, as in a school for youngchildren Compounds that have been used for control of insects such asmosquitos include DEET (diethyl toluamide) and some terpenoids, asreported by Hwang, et al, J. Chem. Ecol., 11, 1297 (1985); and Ruledge,J. Am. Mosquito Control Assoc. 4, 414 (1988). In the work reported byHwang, et al., a screen done on terpenoids as mosquito repellentindicated that terpenoids are effective repellents. Ruledge notes thatα-terpineol is useful in mosquito repellent. U.S. Pat. No. 29,829 toBordenca, et al., discloses that lower hydroxyalkyl amines in which atleast one of the amino hydrogens is replaced by an acyclic monoterpenylradical or hydrogenated acyclic monoterpenyl radical are useful insectrepellents. U.S. Pat. No. 4,193,986 to Cox, U.S. Pat. No. 4,759,930 toGranirer, et al., U.S. Pat. No. 4,671,960 to Thielen, et al., and U.S.Pat. No. 4,587,123 to Price claim that eucalyptus oil is an effectiveflea repellant.

None of these repellents is specific for lice nor proven to beefficacious.

It is therefore an object of the present invention to provide repellentsfor lice that are safe, efficacious, pleasant smelling, and relativelyinexpensive, but which do not contain toxic insecticides.

It is another object of the present invention to provide such repellentsthat are effective in a variety of carriers, including hair sprays,shampoos, and powders.

It is still another object of the present invention to provide suchrepellents that are effective in repelling both human and animal lice.

SUMMARY OF THE INVENTION

It has been discovered that terpenoids, especially terpenoid-alcohols(terpene-ols) and terpenoid-esters, and some aldehydes and ketones ofterpenes, in a concentration of between 0.01% and 50%, most preferablybetween 0.01% and 10 %, are very good lice repellents. Most perfumes anda number of essential oils containing a high content of terpene-ols andesters, greater than 40%, are also very good lice repellents, includingbergamot, sage, styrax, peppermint, and pine siberian.

The active agent can be combined with a pharmaceutically and/orcosmetically acceptable carrier for topical administration, such as anaqueous or alcohol solution, a gel, cream, or a powder, and administeredwith or without additives such as other insect repellents, agentsincreasing solubility or delaying release of active agents,antimicrobial preservatives, antioxidants and fragrances. A number ofagents for delaying release of substances have been developed, includingbiodegradable natural or synthetic polymeric microparticles (includingmicrospheres and microcapsules), liposomes, cyclodextrins, varioussurfactants, and polymers decreasing the volatility of the terpenes.

Examples demonstrate efficacy in in vitro and in in vivo testing.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph of the time dependent repellency of LICE-FREE-SPRAY ofexample 3, plotting % repellency against hours.

FIG. 2 is a graph of the time dependent repellency of LICE-FREE-GEL ofexample 3, plotting % repellency against hours.

FIG. 3 is a graph of the time dependent repellency of LICE-FREE-DECOLOGNE of example 3, plotting % repellency against hours.

FIG. 4 is a graph of the % repellency over time (hours) of thelice-repellent shampoo and lice-repellent conditioner of example 4, ascompared with controls not containing terpenes.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based on the discovery that terpenes, topicallyapplied to the hair and skin, will effectively repel lice. Certainclasses of the terpenes are more effective and therefore commerciallyuseful. Effective concentrations are low enough that the preparationsare not unpleasant in their smell or appearance. An effective amount ofterpene or terpenes can also be combined with a number of aqueous andnon-aqueous formulations and still be effective.

Terpenes are well known naturally occurring unsaturated hydrocarbons(C₁₀ H₁₆) found in many essential oils and oleophilic plant resins. Asused herein, "terpene" includes the saturated derivatives of theunsaturated hydrocarbons as well as mixtures of terpenes. "Terpenoids"includes terpenes and terpenes having a functional group, such as ahydroxy, aldehyde, ketone, or ester.

The carbon backbone of terpenes are formed exclusively of head to taildimerization products of isopentyl (isoprene) units. There are threeprincipal monoterpene hydrocarbon backbones: ##STR1##

Many of these compounds are commercially available. Methods forsynthesis of others are also known to those skilled in the art. Examplesof references books containing methods of synthesis include Chemistry ofTerpenes and Terpenoids. A. A. Newman, ed., (Academic Press, London andNew York, 1972), and references cited therein, the teachings of whichare incorporated therein.

Terpenoid-alcohol or Terpene-ols are terpenoids which have at least onehydroxyl group. Examples of terpene-ols include: C₁₀ H₁₆ O compounds,perillyl alcohol, carveol, myrtenol, and cis-verbenol; C₁₀ H₁₈ Ocompounds, myrtanol, iso-pinocampheol, dihydrocarveol, isopulegol,terpineol, terpinen-4-ol, nerol, geraniol, and linalool, and C₁₀ H₂₀ Ocompounds, menthol, β-citronellol, and dihydro-myrcenol

Terpenoid-esters are terpenoids which have at least one ester groupwhich is the product of the bonding of the hydroxyl group of aterpene-ol with an aliphatic carboxylic acid that can contain functionalgroups such as the hydroxyl or amine on the aliphatic chain. Examples ofsuitable aliphatic carboxylic acids include acetic acid, propionic acid,lactic acid, and various amino acids. Examples of terpenoid-estersinclude: carvyl acetate, carvyl propionate, and menthyl lactate.

The most potent group of repellents are the terpene-ols. Esters ofterpene-ols are potent, as well. Essential oils which contain terpenoidsand perfumes which contain terpenoids are also useful. Examples ofessential oils which have high content of terpene-ols and esters:Bergamot (62%); Sage (>50%); styrax (>50%); Peppermint (>50%); PineSiberian (75%). Terpenes, aldehydes and ketones vary in their usefulnessbut as a general group have potential as lice-repellent.

Any concentration above 0.01% will repel lice. The preparations testedin vivo (including clinical trials) contained 0.1-5% by weight, and werefound to be effective. Since high concentrations of the terpenoids havevery strong odors, concentrations above 50% are not useful. Goodprotection can be obtained in the range of 0.01-50%, most preferablybetween 0.1 and 10% by weight.

The following groups of additives can be incorporated in a licerepelling preparation in addition to the terpenoids:

a. Other insect repellents, such as dimethyl phthalate and DEETdimethyl-toluamide).

b. Materials which can improve the effect of the terpenoids, forexample, low molecular weight alcohols, which enhance volatility of theterpenoids.

c. Release and controlled delivery materials which can prolong the timeof action, for example by way of microencapsulation which results inslow release. Additives of this nature include various surfactants. Anumber of agents for delaying release of substances have been developed,including biodegradable natural or synthetic polymeric microparticles(including microspheres and microcapsules), liposomes, cyclodextrins,various surfactants, and polymers decreasing the volatility of theterpenes.

d. Formulation materials, which include solvents, surfactants,antimicrobial preservatives, antioxidants and fragrance materials.

The active ingredients can be incorporated in any kind of topicalpreparation, such as a spray, liquid, gel, cream, shampoo, conditioner,or mousse. Several examples are provided. Many additional preparationsare known to those skilled in the art or commercially available.

Four methods were employed in order to determine the efficacy of activesubstances and finished products: three laboratory tests and one fieldtrial. The procedures are described below in the following non-limitingexamples. It is important to emphasize that the three laboratory methodsare different in procedures and conditions and hence differ in theirabsolute results. As a rule, method 1 is more facile and gives morereproducible results versus method 3 and thus is preferable as a qualitycontrol bioassay.

EXAMPLE 1 Screening of Compounds for in vitro lice-repellency

Screening tests were performed on many substances of the followinggroups: terpenes (hydrocarbons), terpenoid alcohols, terpenoid esters,terpenoid aldehydes and ketones, essential oils which contain terpenoidsand perfumes which contain terpenoids, as well as various general insectrepellents, for lice-repellency. Each experiment included exposure ofthe lice to different concentrations of the tested substance, andmeasuring the dose response of those materials.

Standard in vitro Test on Filter Paper

A petri-dish method was used to examine the repellency of the solutionsfor lice. A filter paper (Whatman No. 4, 5.5 cm in diameter) was securedin a petri-dish. A 100 μl portion of the test solution was placed on acorduroy patch (1.5 cm²). The material was allowed to dry for 30 min. atroom temperature (20±3° C.) and the patch was placed at the periphery ofthe petri-dish. A patch treated with a control solution (96% Ethanol)was placed on the opposite side of the dish. Twenty female lice whichhad been fed 24 hours previously were placed in the middle of the dish.A box was placed over the dish and it was covered with a dark cloth inorder to keep the test area in the dark. The experiment was carried outat room temperature (20°±3° C.) and lasted 10 min. The number of lice onthe treated and controlled patches as well as on the area between thepatches was recorded in a protocol. The experiment was repeated threetimes for each sample.

% repellency was calculated by the following formula:

    % REPELLENCY=(1-T/C)×100

where: T=number of lice on the treated patch

C=number of lice on the untreated patch

The following terms were recorded:

RC₈₀ =Concentration giving 80% repellency.

RC₅₀ =Concentration giving 50% repellency.

RD₈₀ =mg/cm² giving 80% repellency.

RD₅₀ =mg/cm² giving 50% repellency.

The results are summarized as follows:

Terpenes: Five terpenes, as shown in Table 1, were tested. They aremoderate repellents Typical RC-80 is 1-4% and typical RD-80 1-3 mg/cm².

Terpenoid--alcohols ("Terpene-ols"): Sixteen terpene-ols, as shown inTable 1, were tested. They all repel lice. They are good to excellentrepellents, having typical RC-80 values between 0.02-1, and typicalRD-80 of 0.01-1.

Terpenoid--esters: Four esters were tested. All of them are goodrepellents, having RC-80 values between 0.1-0.8, and RD-80 valuesbetween 0.07-0.5.

Terpenoid--aldehyde and ketones: Seven of these were tested. They allrepel lice, but the range of activity is wide: some are very good andsome are poor (see Table 1).

Essential oils which contain terpenoids and perfumes which containterpenoids: Ten essential oils were tested with lice, and in parallelwere analyzed by GC-Mass Spectrography. Eight of the oils containterpene-ols in high concentration (more than 40%). Those which containterpene-ols are good repellents having RC-80 values between 0.7-1.5, andRD-80 values between 0.5-1.

The results for terpene-ols, terpene-esters, other terpenoids andessential oils which contain terpenoids are shown in Table 1.

                  TABLE 1                                                         ______________________________________                                        RC and RD Values of Terpenoids                                                                               RD.sub.80  RC.sub.50                           TYPE OF   NAME OF       RC.sub.80                                                                            mg/   RC.sub.50                                                                          mg/                                 COMPOUND  COMPOUND      (%)    cm.sup.2                                                                            (%)  cm.sup.2                            ______________________________________                                        TERPENE-OL                                                                              CARVEOL        1.500  1.050                                                                              0.600                                                                              0.420                                         PERILLIL       0.030  0.020                                                                              0.010                                                                              0.007                                         ALCOHOL                                                                       Cis VERBENOL   2.000  1.400                                                                              1.000                                                                              0.700                                         MYRTENOL       0.900  0.630                                                                              0.500                                                                              0.350                                         DIHYDRO        0.900  0.630                                                                              0.400                                                                              0.280                                         CARVEOL                                                                       ISOPULEGOL     0.800  0.560                                                                              0.500                                                                              0.350                                         Cis MYRTANOL   1.000  0.700                                                                              0.600                                                                              0.420                                         NEROL          0.800  0.560                                                                              0.500                                                                              0.350                                         β-CITRONELLOL                                                                           0.070  0.049                                                                              0.020                                                                              0.014                                         α-TERPINEOL                                                                            0.080  0.056                                                                              0.040                                                                              0.028                                         GERANIOL       0.020  0.014                                                                              0.005                                                                              0.004                                         LINALOOL       0.080  0.056                                                                              0.020                                                                              0.014                                         MENTHOL        0.150  0.105                                                                              0.030                                                                              0.021                                         DIHYDRO        0.800  0.560                                                                              0.600                                                                              0.420                                         MYRCENOL                                                                      ISOPINO-       0.300  0.210                                                                              0.200                                                                              0.140                                         CAMPHEOL                                                                      TERPINEN-4-OL  0.090  0.063                                                                              0.020                                                                              0.014                               TERPENE-  MENTHYL        0.100  0.070                                                                              0.050                                                                              0.035                               ESTER     LACTATE                                                                       CARVYL         0.600  0.420                                                                              0.200                                                                              0.140                                         PROPRIONATE                                                                   ISO BORNYL     0.800  0.560                                                                              0.600                                                                              0.420                                         ACETATE                                                                       DIHYDROCARVYL  0.300  0.210                                                                              0.150                                                                              0.105                                         ACETATE                                                             TERPENE   β PINENE  1.100  0.770                                                                              0.200                                                                              0.140                                         α TERPINENE                                                                            1.500  1.050                                                                              0.900                                                                              0.630                                         CARENE         2.000  1.400                                                                              1.000                                                                              0.700                                         + LIMONENE     3.000  2.100                                                                              2.000                                                                              1.400                                         - LIMONENE     4.000  2.800                                                                              3.000                                                                              2.100                               ESSENTIAL BERGAMOT       0.700  0.490                                                                              0.200                                                                              0.140                               OIL       CLAY SAGE      0.800  0.560                                                                              0.200                                                                              0.140                                         STYRAX         0.200  0.140                                                                              0.100                                                                              0.070                                         PEPPERMINT     1.000  0.700                                                                              0.300                                                                              0.210                                         PINE SIBERIAN  1.500  1.050                                                                              0.900                                                                              0.630                               ALDEHYDE &                                                                              CITRAL         0.600  0.420                                                                              0.300                                                                              0.210                               KETONE    IONONE         0.600  0.420                                                                              0.250                                                                              0.170                                         DIHYDRO        0.500  0.350                                                                              0.200                                                                              0.140                                         CARVONE                                                                       PULEGONE       0.700  0.490                                                                              0.400                                                                              0.280                               ______________________________________                                         RC = Repellency concentration = (1 - T/C) × 100                         T = Number of lice on the treated patch                                       C = Number of lice on the untreated patch                                     RD = Repellency dosage in mg/cm.sup.2                                         RC.sub.80 = Concentration giving 80% repellency                               RC.sub.50 = Concentration giving 50% repellency                               RD.sub.80 = mg/cm.sup.2 giving 80% repellency                                 RD.sub.50 = mg/cm.sup.2 giving 50% repellency                            

These results lead to the following conclusions:

1. The most potent group of repellents are the terpeneols.

2. Esters of terpene-ols are potent as well.

3. Essential oils which contain terpenoids and perfumes which containterpenoids are also useful. Examples of essential oils which have highcontent of terpene-ols and esters: Bergamot (62%); Sage (>50%); Styrax(>50%); Peppermint (>50%); Pine Siberian (75%).

4. Aldehydes and ketones of terpenes vary in their usefulness but as ageneral group have potential as lice-repellents.

Any concentration above 0.01% will repel lice.

EXAMPLE 2 In vitro testing of lice repellency on hair to compareeffectiveness against body and head lice

A bundle of human hair (10 cm long) were dipped into the repellentsolution, containing 52% purified water, 44% alcohol, 2% terpineol and2% peppermint oil, until it was half way immersed and held there forfive seconds. The hairs were then dried for one hour at roomtemperature. The ends of the hairs were held in position on double sidedsticky tape on a petri dish. Ten lice were placed in the center of thehairs between the treated and untreated areas. This was done in a darkroom and the direction of movement of the lice was followed with the aidof an infra-red lamp, and recorded in a protocol. The experiment wasrepeated three times for each sample.

The results were as follows:

    ______________________________________                                                       Treated area                                                                           Untreated area                                        ______________________________________                                        Head lice (mean value)                                                                         3          7                                                 Body lice (mean value)                                                                         3.5        7.5                                               ______________________________________                                    

It was concluded on the basis of these results that head lice and bodylice are similarly repelled by the product.

EXAMPLE 3 In vivo test of lice repellency on rabbits

Body lice were reared in the laboratory by feeding them every 48 hourson rabbits. Lice were placed on the shaved abdomen of a white rabbit andleft until they fed to satiety. Outside the host the lice weremaintained at a temperature of 30 ±1° C., and relative humidity of70±10%.

The abdomen of a New Zealand white rabbit was shaved and 100 μl of thetest substance was evenly distributed over an area 2.5×5 cm. A glasscylinder 5 cm high with an internal diameter of 3.5 cm was placed on therabbit's abdomen so that one half of it was covering the treated areaand the other half the adjacent untreated area. 40 human body lice(Pediculus humanus humanus) (20 adults and 20 nymphs) which had been fed24 hours previously were placed in the middle of the cylinder betweenthe treated and untreated area, and the cylinder was covered with a darkcloth in order to keep the test area in the dark. The lice remained onthe body of the rabbit for 5 minutes during which time over 95% of themhad started feeding. The number of lice found on the treated area wasthen recorded and the specimen was photographed. Room temperature duringthe test was 20±3° C. For comparison to the tested samples, two controlswere also tested: 70% Ethanol (Frutarom, C. P.) and 33% DimethylPhthalate (in 70% Ethanol).

The products were topically applied as a spray, lotion or gel on humanhair and skin, to repel lice. The above procedure was carried out 1, 3,5, and 24 hours after application of a test substance. Each substancewas tested three times on three different rabbits on three differentoccasions.

The results of the experiments, expressed in percents of efficacy,summarized in Tables 2 and 3, indicate highly effective repellency ofthe three products that were tested for at least 5-7 hours.

The results confirm the in vitro studies, demonstrating the products'efficacy on a living body, under conditions close to those which prevailin humans (skin temperature, humidity, existence of hair andavailability of blood favored by lice). New Zealand white rabbits havethese properties, and they are often used to simulate behavior of liceon humans.

RESULTS

The results of the examinations are presented in Tables 2 and 3, and inFIGS. 1 to 3. FIG. 1 is a graph of the time dependent repellency ofLICE-FREE-SPRAY. FIG. 2 is a graph of the time dependent repellency ofLICE-FREE-GEL. FIG. 3 is a graph of the time dependent repellency ofLICE-FREE-DE COLOGNE.

The products tested were:

LICE-FREE SPRAY contains: 50% purified water, 42% alcohol, 2%diethyltoluamide, 2% diethylphthalate, 2% terpineol and 2% styrax oil.

LICE-FREE GEL contains 46.6% purified water, 45% alcohol, 2% diethyltoluamide, 2% methyl lactate, 2% menthol, 0.9% Carbomer® 940, and 1.5%Triethanolamin.

LICE-FREE-DE-COLOGNE contains: 50% purified water, 44% alcohol, 2%citronellol, 2% carvyl acetate and 2% bergamot oil.

                  TABLE 2                                                         ______________________________________                                        Number of Lice (Out of 40) Found in the                                       Treated Area (results are presented in triplicate)                                             Time (hours)                                                 Product            1      3      5    7   24                                  ______________________________________                                        LICE-FREE - SPRAY                                                                              (a)   1      1    4     3  19                                                 (b)   5      4    4     4  14                                                 (c)   6      6    6     5  21                                LICE-FREE GEL    (a)   3      5    4     9  21                                                 (b)   5      8    3    10  19                                                 (c)   8      7    8    10  19                                LICE-FREE-DE COLOGNE                                                                           (a)   3      5    4     7  18                                                 (b)   1      6    4     6  21                                                 (c)   7      5    7     5  20                                Control 1 - 70% Ethanol                                                                        (a)   18     16   17   17  N.D.                                               (b)   18     20   22   25  N.D.                                               (c)   18     21   19   18  N.D.                              Control 2 - 33% D.M.P.                                                                         (a)   21     16   16   18  N.D.                                               (b)   12     18   14   14  N.D.                                               (c)   15     20   18   12  N.D.                              ______________________________________                                         (a)  First experiment                                                         (b)  Second experiment                                                        (c)  Third experiment                                                         N.D.  Not Determined                                                          D.M.P.  Dimethyl Phthalate                                                    % Repellency was calculated according to equation 1.                          ##STR2##                                                                      Where: A = Total Number of lice                                               n = Mean number of lice found in the treated area                             ##STR3##                                                                 

According to Equation 1, when lice are evenly distributed between thetreated and untreated areas (n=1/2 A), % Repellency=0, and when no liceare left in the treated area (n=0), % Repellency=100.

The mean % Repellency values, calculated for LICE-FREE products arepresented in Table 3 and FIGS. 1-3.

                  TABLE 3                                                         ______________________________________                                        % Repellency of "LICE-FREE" products (Mean Values)                                               % Repellency                                               Product              1     3       5   7                                      ______________________________________                                        LICE-FREE SPRAY      80    82      77  80                                     LICE FREE GEL        73    67      75  50                                     LICE-FREE DE COLOGNE 82    73      75  68                                     Control 1 (70% Ethanol)                                                                            10     5       3   0                                     Control 2 (Dimethyl Phthalate)                                                                     20    10      20  26                                     ______________________________________                                    

The time dependant repellency of the three products is presented inFIGS. 1-3.

Treatment with LICE-FREE--SPRAY resulted in 77-82% repellency againstlice for a duration of at least 7 hours.

Treatment with LICE-FREE--GEL resulted in 67-75% repellency against licefor a duration of at least 5 hours.

Treatment with LICE-FREE--DE COLOGNE resulted in 68-82% repellencyagainst lice for a duration of at least 7 hours.

For comparison, the insect repellent, Dimethyl Phthalate gave poorresults (10-25% repellency) and in the control of 70% Ethanol norepellency was found.

On the basis of this study it can be concluded that the three products,LICE-FREE SPRAY, LICE-FREE GEL and LICE-FREE - DE COLOGNE are effectiveas lice repellents for at least 5-7 hours.

EXAMPLE 4 Demonstration of efficacy of lice-repellant shampoo andconditioner

The efficacy of a shampoo and a hair-conditioner, aimed at repellency ofhuman lice was examined in an in vivo procedure on rabbits. Eachexperiment included a terpenoid containing product and four controls:70% Ethanol, Dimethyl phthalate, placebo shampoo and placeboconditioner. All experiments were repeated three times, and the resultswere consistent, as shown by Table 4.

The following products were tested:

SHAMPOO contains 56.15%, purified water, 12% TEA Lauryl, Sluphate (40%),14% Cocamphoglycinate (and) Sodium Trideceth Sulphate (35%), 8% Sodiumlaureth sulphate (27%), 2% Lauramide DEA (85%), 2% Terpinen-4-ol, 2%α-Terpineol, 2% Perillyl alcohol, 1% Glycol Monostearate, 0.4% CitricAcid, 0.25% Fragrance, 0.2% Preservatives.

CONDITIONER contains 79.8% purified water, 7% protein hydrolysate, 6%Cetrimonium chloride (25%), 1.5% Vitamin F, 2.8% PEG-150 Stearate, 2%Cetyl Alcohol, 0.2% Preservatives, 0.2% Geraniol, 0.5% Cetyl Alcohol,0.2% Preservatives, 0.2% Fragrance.

                  TABLE 4                                                         ______________________________________                                        Number of Lice (Out of 40)                                                    Found in the Treated Area                                                                          Time (hours)                                             Product                1     3      4   7                                     ______________________________________                                        LICE-FREE - SHAMPOO     5     7      8  10                                                            8     8     10  11                                                            5     8      7  10                                    LICE-FREE - CONDITIONER                                                                               7    10     11  12                                                            8     8      9  12                                                            9     9     10  12                                    Control 1 - 70% Ethanol                                                                              10    20     19  22                                                           19    22     22  26                                                           20    18     22  24                                    Control 2 - 33% D.M.P. 21    16     16  18                                                           12    18     14  14                                                           15    20     18  12                                    Control 3 - PLACEBO SHAMPOO                                                                          15    17     19  22                                                           16    18     20  22                                                           16    22     20  21                                    Control 4 - PLACEBO CONDITIONER                                                                      16    18     19  21                                                           17    18     22  22                                                           16    20     20  23                                    ______________________________________                                         D.M.P.  Dimethyl Phthalate                                                    % Repellency was calculated according to equation 1.                     

According to Equation 1, when lice are evenly distributed between thetreated and untreated areas (n=1/2 A), % Repellency=0, and when no liceare left in the treated area (n=0), % Repellency=100.

The mean % Repellency values are presented in Table 5.

                  TABLE 5                                                         ______________________________________                                        % Repellency of "LICE-FREE" products (Mean Values)                                               % Repellency                                                                  After Time (hours)                                         Product              1     3       5   7                                      ______________________________________                                        LICE-FREE SHAMPOO    70    62      58  48                                     LICE-FREE CONDITIONER                                                                              60    55      50  40                                     Control 1 (70% Ethanol)                                                                             5     3       2   0                                     Control 2 (Dimethyl Phthalate)                                                                     20    10      20  26                                     Control 3 (Placebo Shampoo)                                                                        22     8       2   0                                     Control 4 (Placebo Conditioner)                                                                    18     7       2   0                                     ______________________________________                                    

FIG. 4 is a graph of the % repellency over time (hours) of thelice-repellent shampoo and lice-repellent conditioner, as compared withcontrols not containing terpenes.

The results indicate moderate to high effectiveness lasting for 3 to 5hours. The duration of effectiveness of the shampoo and conditioner wereshorter than the duration of the spray.

EXAMPLE 5 Field trial testing of effectiveness of lice repellency onschool age children

The product "Lice Free", intended for the prevention of liceinfestation, containing 50% purified water, 42% alcohol, 2% % DiethylToluamide, 2% Diethyl Phthalate, 2% Terpineol, and 2% Styrax essentialoil, was examined in a controlled field study. This study, afterreceiving the authorization of the Helsinki Committee, was conducted bythe Kaplan Hospital, Pediatric Department A, under the leadership ofProf. Y. Barak. After receiving the consent of the children's parents,the children were diagnosed according to their state of pediculosis.

In order to carry out this study, a group of one hundred twenty ninechildren were selected who met the criteria detailed in the studyprotocol. The study was carried out at two sites: Kibbutz Masu'otItzhak, performed by nurse Rivka Nadivi, and in Zefat, performed bynurse Raya Sho'an. The participants were divided into a "test group" anda "control group". The Test group consisted of sixty two children andthe control group consisted of sixty seven children.

The results of this trial indicated that the probability of liceinfestation in a child is 14.9 times greater if the product is notapplied. This means the product gives excellent protection against liceinfestation.

Materials and Methods

The test product, containing 50% purified water, 42% alcohol, 2% DiethylToluamide, 2% diethyl phthalate, 2% Terpineol, and 2% Styrax essentialoil, was provided to the nurses. The product is presented in a spraybottle, equipped with a nozzle of 0.10 ml. The control product,containing 50% purified water and 50% alcohol, was provided in bottlessimilar to the test product. According to the protocol, the users wereinstructed to spray four to eight spray strokes (0.40-0.80 ml), twice aday (morning and noon) on a child's hair, and then distribute theproduct by hand or by a regular hair brush throughout the hair.

Definitions, Postulates and Instructions

The following definitions, postulates, and instructions were made:

Pediculosis--A state in which a person bears lice or lice eggs on hishead.

Low state of infestation--Less than 10% of the population havepediculosis.

Medium state of infestation--10-20% of the population have pediculosis.

High state of infestation--Above 20% have pediculosis.

Protection factor--A number expressing the ratio between the rates ofinfestation in the untreated group vs. the treated group. ##EQU1## Asper the advice of Dr. K. Mumcuoglu of the Hebrew University MedicalSchool, Department of Parasitology, the implication of the value of theprotection factor is as follows:

    ______________________________________                                        1      means "No Protection";                                                 3      means "Low-Medium Protection" (reducing the                                   probability of infestation three times);                               5      means "High Protection" (reducing the probability                             of infestation five times); and                                        7      more means "Excellent Protection".                                     ______________________________________                                    

For example, a protection factor of 6 indicates a state in which theprobability of lice infestation in a child is six times greater withoutapplying the product.

According to the information received from the Ministry of Health, theaverage national affliction rate in Israel is 15-20%. The main afflictedpopulation included children between the ages of two and twelve. In anaverage Israeli home a child is examined weekly or biweekly and istreated based on his/her needs.

The population for a given study included only children of a set agerange (±2 years). During the period of study, no other lice product wasused by the participants. Children having any scalp diseases were notallowed to participate. The study took place in groups having amedium-high state of infestation.

The following details were recorded for each participant: age, gender,weight, height, number of siblings, color of hair, length of hair. Inorder to avoid participants who have individual immunity to liceinfestation, the study excluded children who reported that they hadnever had lice.

All participants were examined for the state of pediculosis. Thediagnosis prior to and after the study were handled by the samepersonnel. Children already infested by lice and/or eggs and childrenwith any type of scalp disease were not treated. Children without liceand/or eggs received numbered bottles of the product (test or control)in a randomized manner. Each child was treated twice a day, five to sixhours apart, according to instructions on the bottle: "Spray four toeight spray strokes on hair and comb with a regular comb". Eachparticipant was checked again at the end of the study and the status ofhis/her pediculosis noted. If irritation occurred, as per each child'sanswers to questions, it was also noted.

    ______________________________________                                               Test Group: Total 62 Children:                                                13 (20.7%) boys;                                                              49 (79.3%) girls                                                              33 (53.2%) aged 2-5 years;                                                    23 (37.1%) aged 6-9 years                                                      6  (9.7%) aged 10-13 years;                                                  15 (24.2%) have fair hair;                                                    47 (75.8%) have dark hair;                                                    37 (59.7%) have short hair;                                                   25 (40.3%) have long hair                                                     Control Group: Total 67 Children                                              44 (65.7%) boys;                                                              23 (34.3%) girls                                                              43 (64.2%) aged 2-5 years;                                                    20 (29.8%) aged 6-9 years;                                                     4  (6.0%) aged 10-13 years                                                   30 (44.8%) have fair hair;                                                    37 (55.2%) have dark hair                                                     38 (56.7%) have short hair;                                                   29 (43.3%) have long hair                                              ______________________________________                                    

State of infestation at beginning of study: Medium-High (>20%).

RESULTS

Out of the 62 participants of the test group, one child was infested(1.6%). Out of the 67 participants of the control group, 16 childrenwere infested (23.8%). The calculated protection factor value was: (23.8/1.6)=14.9, indicating that the product gave excellent protection.

Since out of the test group only one child was infested, the analysisaccording to sectors of participants was statistically meaningless.During the course of the study no internal or external side effects werenoted in the treated children. The status of the children was followedfor a period of three months from the beginning of the study. Duringthis period, no complaints of irritations, allergic reactions,photo-sensitivity or any other irregular occurrences were received. Fromstudying the product components and as per the above mentionedfollow-up, no health problem is expected from applying the product.

Modifications and variations of the present invention, a method andcompositions for preventing lice infestation, will be obvious to thoseskilled in the art from the foregoing detailed description. Suchmodifications and variations are intended to come within the scope ofthe appended claims.

We claim:
 1. A method to repel lice, comprising applying to a human oran animal susceptible to lice infestation an effective amount of aterpenoid or a mixture of terpenoids in an acceptable carrier fortopical application to a human or an animal to repel lice withouttoxicity to the human or animal, wherein the terpenoid is selected fromthe group consisting of terpene-ols not including linalool,terpene-esters, unsaturated terpene, terpenoids containing an aldehydefunctional group, and terpenoids containing a keytone functional group.2. The method of claim 1, further comprising providing the terpenoid ormixture of terpenoids in an acceptable carrier in a concentration ofapproximately between 0.01% and 50% by weight.
 3. The method of claim 2,wherein the carrier comprises a terpenoid or mixture of terpenoids in aconcentration of approximately between 0.01% and 10%.
 4. The method ofclaim 1, wherein the carrier comprises an oil containing greater than40% terpenoid by weight.
 5. The method of claim 4, wherein the oil is aperfume.
 6. The method of claim 1, wherein the unsaturated terpenoid isselected from the group consisting of terpinene, pinene, limonene,myrcene, and carene.
 7. The method of claim 1, wherein the terpene-ol isselected from the group consisting of perillyl alcohol, carveol,myrtenol, cis-verbenol, myrtanol, isopinocampheol, dihyrocarveol,isopulegol, terpineol, terpinen-4-ol, nerol, geraniol, menthol,β-citronellol, and dihydromyrcelnol.
 8. The method of claim 1, whereinthe terpene-ester is selected from the group consisting of carvylacetate, carvyl propionate, menthyl lactate, and iso bornyl acetate. 9.The method of claim 1, wherein the terpenoid aldehyde is selected fromthe group consisting of cytral and neral.
 10. The method of claim 1,wherein the terpenoid ketone is selected from the group consisting ofionone, dihydro carvone, and pullegone.
 11. The method of claim 1,wherein the carrier is a material selected form the group consisting ofan aqueous solution, an alcohol solution, a gel, a cream, a powder,spray, shampoo, conditioner, and hair styling mousse.
 12. The method ofclaim 1, wherein the carrier further comprises a compound selected fromthe group consisting of antimicrobial preservatives, antioxidants,repellents for insects other than lice, fragrances, substancesincreasing binding of terpenes to hair, and substances delayingdissolution of the terpenes.